AB0067 INTERLEUKIN-1 RECEPTOR ANTAGONIST: RELATION TO CARDIOVASCULAR DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: C. Almeida, J. C. Quevedo-Abeledo, L. Cáceres Martín, V. Hernández Hernández, A. Delgado-González, I. Ferraz-Amaro
Journal: Annals of the Rheumatic Diseases (2022)

Background The interleukin-1 receptor antagonist (IL1-Ra) belongs to the IL-1 family. IL1-Ra has an inhibitory function on the inflammatory reaction consisting of preventing the binding of IL-1α and β to their respective receptors. IL-1, in its different subtypes, has been implicated in the pathogenesis of both rheumatoid arthritis (RA) and cardiovascular disease (CV) in the general population. Objectives In the present work we aim to study the relation of IL1-Ra serum levels to RA’s features, and its CV comorbidity and subclinical carotid atheromatosis in a large RA cohort. Methods This was a cross-sectional study that included 430 RA patients. A complete panel of clinical and analytical information related to CV disease was collected: CV risk factors, full lipid profile, insulin and C-peptide serum levels, insulin resistance and β-cell function (%B) indexes by Homeostatic Model Assessment (HOMA2). A carotid ultrasound examination was performed to assess carotid intima-media thickness in the common carotid artery and to detect focal plaque in the extracranial carotid tree. Similarly, IL1Ra and IL-6 serum levels were assessed and disease activity indices, extra-articular manifestations and RA therapies were collected. A multivariable regression analysis was performed to determine how IL1Ra serum levels is associated with disease-related characteristics, CV comorbidity and subclinical atheromatosis in RA patients. Results Regarding CV risk factors, IL1-Ra serum levels were related with waist circumference (coefficient beta -β- 8 [95% confidence interval -CI- 5-11] pg/ml, p&lt; 0.001) and obesity (body mass index &gt;= 30 kg/m2) (β 169 [95% CI 78-260] pg/ml, p&lt;0.001). After adjusting for confounders, IL1-Ra was related with higher levels of several lipid profile molecules, such as total cholesterol (β 12 [95%CI 2-22] mg/dl, p= 0.023), apolipoprotein A1 (β 13 [95% CI 0.5-25] mg/dl, p=0.042) and apolipoprotein C3 (β 3 [95% CI 2-5] mg/dl, p&lt;0.001). Furthermore, higher IL1-Ra serum levels were associated with pancreatic beta cell dysfunction as measured by HOMA2-%B (β 22 [95%CI 2-42], p=0.031). Disease activity using different scores showed a positive relationship with IL1-Ra after multivariable adjustment: DAS28-ESR (β 60 [95% CI 28-92] pg/ml, p&lt;0.001), DAS28-PCR (β 65 [95%CI 26-104] pg/ml, p=0.001) and CDAI (β 99 [95%CI 3-14] pg/ml, p=0.002). Likewise, ESR (β 2 [95% CI 0.07-5] pg/ml, p=0.044) and IL-6 plasma levels (β 3 [95% CI 1-6] pg/ml, p=0.003) were positively associated with IL1-Ra levels after adjusting for covariates. Hydroxychloroquine use, but not other therapies, was associated with lower IL1-Ra serum levels (β -131 [95% CI -260- -2] pg/ml, p=0.046), independently of confounding variables. No association was found between IL1-Ra and intima-media thickness or carotid plaque. Conclusion In RA patients, IL1-Ra serum levels are related to the clinical and biological disease activity, as well as with different CV comorbidities such as dyslipidemia, beta cell dysfunction and obesity. Our findings highlight the beneficial effect that blocking IL-1 activity can have both in the control of RA disease activity and in the management of the CV disease that accompanies the disease. Acknowledgements This work was supported by a grant to JC Q-A. from the Fundación Canaria Instituto de Investigación Sanitaria de Canarias, PI19/00012. Disclosure of Interests None declared